Three-in-One Virus Killer Prevents Common Lethal Infections

A unique combination therapy considerably reduces the infection rate of three viruses--and risk of death--in transplant patients with compromised immune systems.

These results, to be published in the November 1, 2006, issue of the journal Nature Medicine, come from a study conducted at Baylor College of Medicine (BCM), The Methodist Hospital, and Texas Children's Hospital (all based in Houston, TX, USA).

The phase 1 trial, funded by the U.S. National Heart, Lung, and Blood Institute, one of the National Institutes of Health (Bethesda, MD, USA), evaluated the first multivirus killer of its type, called Trivirus-specific cytotoxic T lymphocytes (CTLs), which control infections caused by three commonplace viruses--cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus. Although benign in individuals with healthy immune systems, the viruses can cause life-threatening illnesses in transplant patients and others with compromised immune systems.

The CTLs proved successful and safe in all 11 bone-marrow-transplant patients, who recovered completely within two to four weeks of being treated without any side effects or toxicity. Preexisting therapies for adenovirus have had little success--there is an 80% chance of death following the development of adenovirus.

"Not only were patients prevented from getting these infections after transplant, but those patients who had infections responded to the T-cell therapy and did not require any other treatment,” said senior author Dr. Catherine Bollard, assistant professor of pediatrics, immunology, and medicine at BCM and a researcher at the Center for Cell and Gene Therapy at BCM, Methodist and Texas Children's. "To make dramatic recoveries like these was really quite something.”

The researchers collected cells from bone marrow donors and "trained” T-cells to target the three viruses before injecting them into transplant recipients. "Drugs only control the virus. They don't cure the underlying problem,” said Dr. Bollard. "Whereas by introducing these specialized T-cells, we are fixing the underlying problem. Using your own immune system is preferable to chemical agents, which can have toxic side-effects.”

Although the CTLs must undergo additional testing, the early results suggest the combination therapy to be more cost-effective, and safe than conventional therapies and more efficient than cell-based therapies that target EBV and CMV separately, both of which are carried in about 80% of all people. Adenoviruses are common viruses carried in all populations.

"There is no safe and effective therapy for patients with adenovirus infections at the moment, so if you get an infection after a transplant it becomes very problematic,” said first author Dr. Ann Leen, BCM instructor of pediatrics at the Center for Cell and Gene Therapy. "So we trained certain T-cells to target this virus.”

Dr. Bollard foresees one day expanding the application of CTLs to other individuals with compromised immune systems, including cancer patients undergoing chemotherapy. The therapy could also potentially be used in infants, who are more vulnerable to adenovirus infections than other age groups.



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